Tendons and ligaments are the tough fibers that connect muscle to bone or bone to bone, but tendons and ligaments can be ruptured, severed, or detached from the bone for a variety of reasons. Such tendon or ligament injuries may generally occur due to or resulting from direct trauma to the affected tendon/ligament, weakening of the tendon/ligament due to advanced age, eccentric loading, repetitive motions, overuse and/or increased stress or activity. Such acute injuries are quite dramatic and usually leave the individual unable to move the affected joint.
The most common areas of tendon rupture, tendon severance, or detachment from the bone are (1) the quadriceps (a group of four muscles, the vastus lateralis, vastus medialis, vastus intermedius, and the rectus femoris) which come together just above the kneecap (patella) to form the patellar tendon; (2) the Achilles tendon, located on the back (posterior) portion of the foot just above the heel. The Achilles tendon serves as the attachment of the calf muscle (gastrocnemius muscle) to the heel of the foot (the calcaneus bone); (3) the rotator cuff, located in the shoulder and composed of four muscles (the supraspinatus (the most common tendon ruptured), infraspinatus, teres minor, and subscapularis); (4) the biceps of the arm, which functions as a flexor of the elbow. Ruptures of the biceps are classified into proximal (close) and distal (far) types; and (5) the flexor tendons of the hand, such as the flexor brevis and longus. The most common areas of ligament rupture, ligament severance, or detachment from the bone are the anterior cruciate ligament (ACL), posterior cruciate ligamen (PCL), and medial collateral ligament (MCL). For almost all tendon and ligament injuries there may be consideration pain (either acute or chronic), loss of motion and weakness of the affected joint or limb. For a ruptured or detached tendon/ligament, surgery is the most common course of treatment, in order to secure the tendon or ligament to its bone, or to reconnect the ruptured or severed ends of the affected tendon/ligament. For other tendon/ligament injuries, common treatments include rest, ice, NSAIDs, corticosteroid injections, heat, and ultrasound. However, despite decades of research and increasing clinical attention to these injuries, their clinical outcomes remain unpredictable.
With respect to the quadricepts, rupture of the patellar tendon is a relatively infrequent, yet disabling injury, which is most commonly seen in patients less than 40 years of age. It tends to occur during athletic activities when a violent contraction of the quadriceps muscle group is resisted by the flexed knee. Rupture usually represents the final stage of a degenerative tendinopathy resulting from repetitive microtrauma to the patellar tendon.
With respect to the Achilles tendon, both athletes and non-athletes are at risk for developing injuries at all ages, with most injuries occurring in men between the ages of 30 and 50 years of age (Boyden, E., et al., Clin Orthop, 317:150-158 (1995); Hattrup, S, and Johnson, K, Foot and Ankle, 6: 34-38 (1985); Jozsa, L., et al., Acta Orthop Scandinavica, 60:469-471 (1989)). Achilles tendonitis and tendinosis are also common in individuals whose work puts stress on their ankles and feet, as well as in “weekend warriors,” those who are less conditioned and participate in athletics only on weekends or infrequently.
In the case of rotator cuff injuries, notwithstanding advances in surgical instrumentation and techniques, the current techniques fall short of producing an enduring repair, with some studies citing failure rates as high as 94%. Failure of tendon repairs may be attributed to poor healing of the damaged tendon and poor reattachment of the injured tendon to the bone.
A firm attachment of ligament to bone is also essential for many ligament reconstruction procedures. Successful ligament substitution procedures, such as anterior cruciate ligament reconstruction, require fixation of a tendon graft into a bone tunnel and progressive ingrowth of bone into the tendon to create a biological attachment between the bone and the tendon. Histological and biomechanical studies show that it generally requires six to twelve weeks after the transplantation of a tendon graft to a bone to achieve bone ingrowth, tendon-bone attachment, mineralization, and greater collagen-fiber continuity between the tendon and the bone. See, Rodeo S. A. et al., Tendon-Healing in a Bone Tunnel, 75(12): 1795-1803 (1993).
Accordingly, there is a need to provide new compositions and new methods of treatment for various tendon/ligament injuries and tendon/ligament to bone attachment to improve the healing response associated with surgical repairs or other non-surgical treatments.
All references cited herein, including, without limitation, patents, patent applications and scientific references, are hereby incorporated by reference in their entirety.